Dapagliflozin for attenuating early anthracycline-associated cardiac changes (DAPA-AIC): a randomized, double-blind, placebo-controlled trial.

Aims

To evaluate whether dapagliflozin attenuates early cardiac functional and biomarker changes during anthracycline-based chemotherapy. MATERIALS &

Methods

In this randomized, double-blind, placebo-controlled phase II trial, 94 adults were assigned 1:1 to dapagliflozin 10 mg once daily or placebo for 4 months; 90 completed follow-up. The primary endpoint was 4-month left ventricular ejection fraction (LVEF), analyzed using analysis of covariance (ANCOVA) adjusted for baseline LVEF. Secondary and exploratory outcomes included cardiac biomarkers and the early-to-late transmitral flow velocity ratio (E/A ratio).

Results

Dapagliflozin was associated with higher adjusted 4-month LVEF than placebo (adjusted mean difference, 2.40 percentage points; 95% confidence interval [CI], 1.25-3.54; p < 0.001). Change in LVEF was +0.13 ± 2.28 versus -2.31 ± 3.27 percentage points, respectively. E/A ratio decline was attenuated (p = 0.030). Galectin-3 decreased with dapagliflozin but increased with placebo (p < 0.001), while N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased less (p = 0.004). No major safety signal was observed during the 4-month follow-up.

Conclusions

Dapagliflozin was associated with attenuation of early anthracycline-associated cardiac functional and biomarker changes. Larger, longer trials are needed to determine clinical benefit. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov identifier is NCT06888505. Retrospectively registered.